Biomedical subjects

J D Rounds

Publications and source records attributed to J D Rounds.

16 recordsLinked to original sources

PubMed2001

Sepsis increases the plasma membrane content of alpha1 and alpha2 isoforms of Na+-K+ adenosine triphosphatase in rat skeletal muscle.

HYPOTHESIS: Increased Na(+)-K(+) adenosine triphosphatase (ATPase) activity in skeletal muscle during sepsis is caused by transient increases in enzyme content within the plasma membrane. DESIGN: Randomized controlled study. SETTING: University laboratory. INTERVENTION: Eighty-eight adult male Wistar rats were randomly assigned to undergo cecal ligation and puncture (CLP) or sham operation. MAIN OUTCOME MEASURES: Gastrocnemius muscles were harvested 6, 12, 24, and 48 hours after operation and Na(+)-K(+) ATPase activities were measured spectrofluorimetrically. Messenger RNA (mRNA) levels for the alpha1 and alpha2 isoforms of Na(+)-K(+) ATPase were determined by Northern blot analysis. Crude membranes, internal membranes, and purified plasma membranes were isolated from gastrocnemius muscles and protein levels of alpha1 and alpha2 isoforms were determined by Western blot analysis. RESULTS: Na(+)-K(+) ATPase activity in the CLP group was significantly higher compared with the sham group 24 hours after operation (P<.05). However, there were no differences between the sham and CLP groups 6, 12, or 48 hours after operation. No significant differences between the CLP and sham groups were noted in mRNA levels for Na(+)-K(+) ATPase alpha1 and alpha2 isoforms. Western blot analysis revealed that the plasma membrane (but not internal membrane or crude membrane) content of alpha2 and alpha1 isoforms from the CLP group was significantly increased compared with the sham group 24 hours after operation (P<.05). CONCLUSIONS: Na(+)-K(+) ATPase activity increases 24 hours after CLP in gastrocnemius muscle and then declines. This increase is caused by increased Na(+)-K(+) ATPase protein levels in the plasma membrane.

Animals↗

PubMed1999

Hindlimb ischemia-reperfusion increases complement deposition and glycolysis.

BACKGROUND: Hindlimb ischemia-reperfusion (HIR) impairs cellular energy metabolism and causes local muscle injury possibly through free radical or complement-mediated mechanisms. MATERIALS AND METHODS: To determine the relationship among myocellular energetics, histopathological injury, and mediator activity, male Wistar rats underwent 4 h of Sham (n = 8), Unilateral (n = 8), or Bilateral (n = 8) hindlimb ischemia followed by 4 h of reperfusion. All rats underwent 31P magnetic resonance spectroscopy of their right gastrocnemius muscle to determine various high-energy phosphate ratios including ATP to Pi (ATP/Pi, a measure of energy status) and phosphocreatine to Pi (PCr/Pi, a measure of thermodynamic capacity). Gastrocnemius muscles were then harvested to determine muscle damage and complement membrane attack complex (MAC) deposition by immunohistochemical staining [grade 0 (none) to 3 (very severe)] and to measure glutathione (GSH), DNA, and enzyme activities: beta-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, and citrate synthetase. RESULTS: HIR was associated with significant declines in ATP/Pi and PCr/Pi (P < 0.001). Progressively more severe HIR (Sham, Unilateral, Bilateral) was associated with greater MAC deposition (0. 0 +/- 0.0, 1.0 +/- 0.3, 1.5 +/- 0.4, P = 0.06, mean +/- SEM) and histological damage (0.0 +/- 0.0, 0.9 +/- 0.3, 1.3 +/- 0.4, P < 0. 05). GSH levels, beta-hydroxyacyl-CoA dehydrogenase, and citrate synthetase activities were not affected by HIR, but phosphofructokinase activity increased (24.09 +/- 2.42, 35.16 +/- 5. 26, 59.29 +/- 9.82 mmol/mg of DNA/min, P < 0.05). Although GSH levels were not significantly altered, complement deposition was closely associated with skeletal muscle injury and compensatory changes in glycolysis. Alterations in myocellular bioenergetics after HIR closely paralleled complement deposition rather than GSH depletion. CONCLUSIONS: Therapeutic strategies aimed at controlling complement activity and assessment techniques based on bioenergetics may allow more precise determinations of the effects of HIR injury.

Adenosine Triphosphate↗

PubMed1997

Starvation enhances hepatic free radical release following endotoxemia.

Although it is well known that malnourished patients who become septic have an increased risk of organ failure and death compared to normally nourished individuals, the pathological processe(s) underlying this observation are unknown. To evaluate one possible explanation for this finding, we tested the hypothesis that malnutrition depresses hepatic antioxidant stores and accelerates hepatic release of oxygen free radicals in an animal model of sepsis. Male rats were either fasted (n = 14) or fed (n = 14) for 3 days prior to receiving lipopolysaccharide (LPS, 17 mg/kg intraperitoneally). Animals were weighed daily and then sacrificed 6 and 24 hr after LPS administration to determine hepatic superoxide anion (an oxygen free radical) release and liver glutathione (GSH, an antioxidant) content. Fasted rats were severely malnourished as indicated by a 23% decrease in body weight compared to fed rats, which gained 11% (P < 0.05). Liver GSH was depressed by 30% (P < 0.05) and 20% (P = 0.066) in the fasted compared to fed animals 6 and 24 hr after LPS administration. In addition, hepatic superoxide anion release was 210 and 75% higher in the fasted animals 6 and 24 hr after LPS injection (P < 0.05 at both time points). Liver superoxide anion release and GSH content were negatively correlated (P < 0.001, R = - 0.73) indicating that superoxide anion release increased as GSH content fell. Malnutrition leads to depletion of liver antioxidant stores with accelerated release of hepatic oxygen free radicals. Oxidant-mediated organ damage may be one cause of increased morbidity and mortality in malnourished, systemically infected patients.

Animals↗

PubMed1997

Superiority of blood over saline resuscitation from hemorrhagic shock: a 31P magnetic resonance spectroscopy study.

OBJECTIVE: To study the relation between blood and saline administration, postresuscitation hematocrit (Hct) level, and metabolic recovery after hemorrhagic shock. SUMMARY BACKGROUND DATA: It is generally believed that crystalloid can be substituted, in whole or in part, for blood during resuscitation of hemorrhagic shock. This is based on the belief that Hct can be safely reduced but should not fall below a critical level. METHODS: Male rats weighing 200 g were subjected to an isobaric hemorrhagic shock at a mean arterial pressure of 30 mmHg for 14 minutes, after which they were randomized to one of three resuscitation regimens. Control group (n = 36) were resuscitated by return of all shed blood. Mid-Hct (n = 39) and low-Hct (n = 60) groups were depleted of one third and one half of their circulating blood volumes, respectively, and were resuscitated with three times that volume of normal saline. Skeletal muscle intracellular energetics and pH were measured serially using 31P magnetic resonance spectroscopy at baseline, during shock, and after resuscitation. Arterial blood was sampled at the same time points. The number of surviving animals in each group at 24 hours was recorded. RESULTS: After resuscitation, surviving rats in the low-Hct group demonstrated a greater consumption of high-energy phosphocreatine stores than did the other groups (control = 0.479 +/- 0.003, mid-Hct = 0.465 +/- 0.004, low-Hct = 0.457 +/- 0.007, mean +/- standard error of the mean; p < 0.01 low-Hct vs. other groups by analysis of variance). The rats that received saline resuscitation developed a relative intracellular acidosis (control = 7.29 +/- 0.02, mid-Hct = 7.25 +/- 0.02, low-Hct = 7.23 +/- 0.02; p < 0.05 controls vs. other groups by analysis of variance). At 24 hours, the death rates were significantly different among the groups: control = 1 of 36 rats (2.8%), mid-Hct = 6 of 39 (15.4%), and low-Hct = 14 of 60 (23.3%) (p < 0.05 by chi square analysis). CONCLUSION: The oxygen-carrying capacity of resuscitation fluid has an important impact on intracellular metabolism and outcome.

Animals↗

PubMed1996

Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state.

Glutathione (GSH) is the major intracellular antioxidant and is essential to normal cell function and replication. Cysteine and other thiol compounds have been considered rate-limiting for GSH biosynthesis, but recent studies have demonstrated that glutamine (GLN) becomes essential during metabolic stress to replete tissue GSH levels which have become depleted. To determine the role of GLN supplementation in the resting, nonstressed state, we studied three groups of Wistar rats. The animals were catheterized and randomly assigned to one of three groups; (1) chow ad libitum group receiving iv saline (control), (2) standard total parenteral nutrition (STA-TPN) group, and (3) glutamine-enriched TPN (GLN-TPN) group. The intravenously fed animals received no rat chow. The infusions were administered at a rate of 2.2 ml/hr for 4 days and all animals were harvested on the fifth day of study. The GLN-TPN group had a significantly higher plasma GSH level than STA-TPN or control animals (P < 0.01). The hepatic concentration of GSH and the oxidized GSH/reduced GSH were similar in all groups. GLN-TPN had a significantly lower plasma ALT level than the control group (P < 0.05). The control group had a significantly higher ALP level than STA-TPN and GLN-TPN animals (P < 0.01). There were no significant differences in other measures of hepatic functions among the three groups. Our data demonstrate that in this model GLN-enriched TPN enhances plasma GSH concentrations, while maintaining hepatic GSH stores. This suggests that GSH turnover is altered during glutamine-enriched TPN, which may explain how dietary GLN supplementation enhances tissue antioxidant capacity.

Animals↗

PubMed1996

Does multifrequency bioelectrical impedance relate to body composition?

BACKGROUND: There is need for a rapid, noninvasive, inexpensive yet accurate bedside technique to measure body composition. Bioelectrical impedance analysis measures the resistance and conductance of a weak electrical current passed through the body. It has been suggested that multifrequency impedance analysis can determine the distribution of fluid between the extracellular and intracellular compartments. MATERIALS AND METHODS: The correlation between the resistance signals obtained from multifrequency bioelectrical impedance measurements and body composition was determined in normal rats ranging from 150 to 400 g in weight. Total body water, body fat, total body sodium, and total body potassium were measured using the carcass analysis technique, and extracellular water was derived from a dilutional marker using sodium bromide. Fat-free mass was calculated as the difference between body weight and body fat, and intracellular water was derived from total body water and extracellular water. Multifrequency bioelectrical impedance was measured at frequencies ranging from 3 to 300 kHz. Resistance at zero frequency and infinite frequency was calculated using the Cole and Cole equation. RESULTS: Resistance index (i.e., length of the animal2/resistance) was highly correlated with all body compartments (r = 0.879-0.996) at all frequencies. There was also a high correlation among all compartments of the body (r = 0.971--0.999). Because of this high intercorrelation among the body compartments, a specific relationship between the multifrequency bioelectrical impedance signal and a specific compartment was not identified. CONCLUSIONS: Resistance index at any frequency will be correlated with any body compartment in a normal population. The utility of this technique should be determined in situations where there is a disturbance in the relationship between various compartments of the body.

Animals↗

PubMed1996

The enhanced effect of parenteral nutrition on hepatotoxicity.

Recent studies have demonstrated that enteral feedings are associated with decreased morbidity and mortality when compared with parenteral feedings. In this study, we hypothesized that (1) route of feeding affects morbidity and mortality in a model of drug-induced hepatotoxicity and (2) glutamine and polymyxin B, which have been reported to reduce bacterial translocation, attenuate this effect when TPN is used. Male virus-free Wistar rats were divided into six groups receiving: (1) ad libitum chow infused with intravenous (IV) saline (Chow), (2) standard total parenteral nutrition solution administered via gastrostomy (Enteral), (3) standard total parenteral nutrition infused via a central catheter (TPN), (4) standard TPN containing polymyxin B (TPN-PolyB), and (5) glutamine-enriched TPN (TPN-GLN). A final group of animals was not manipulated but harvested at time 0 to serve as controls. The dose of polymyxin B used in this study has previously been shown to significantly reduce bacterial translocation. After 4 d of feeding, all rats received 5% dextrose infusion after an intraperitoneal (IP) injection of acetaminophen (ACM). Rats were sacrificed 0, 6, and 24 h after ACM administration. The TPN group had a lower liver glutathione level after 6 and 24 h, greater levels of liver enzymes after 24 h, and a lower survival rate after 24 h compared with Chow. The Enteral group had less morbidity than TPN but greater morbidity than Chow. Addition of polymyxin B or glutamine had a minimal effect on morbidity or mortality when compared to the TPN group. We conclude that rats receiving IV nutrition have greater morbidity and mortality following a standard hepatic insult than chow-fed rats. We speculate that alteration of microsomal cytochrome P-450 or drug clearance may be related to the benefits of providing nutrients by the gastrointestinal route.

Acetaminophen↗

PubMed1995

The duration of infection modifies mitochondrial oxidative capacity in rat skeletal muscle.

Sepsis increases phosphocreatine (PCr) breakdown and reduces PCr stores in skeletal muscle. To determine if systemic infection impairs mitochondrial function, in vivo 13P magnetic resonance spectroscopy (31P MRS) studies of the gastrocnemius muscle were performed in virus-free male Wistar rats 24 or 48 hr after cecal ligation and 18-gauge needle single puncture (24 degrees CLP, n = 16; 48 degrees CLP, n = 15) or sham operation (24 degrees SHAM, n = 18; 48 degrees SHAM, n = 13). Physiologic saline (6 ml/100 g body wt) was injected intraperitoneally for fluid resuscitation. Water but no food was allowed in all animals. High resolution (8.45 Tesla) 31P MRS spectra, obtained at rest and during exercise using a 1.4-cm surface coil, were used to calculate PCr/ATP, PCr/P(i) ratios, and intracellular pH. Steady-state muscle exercise was induced by supramaximal sciatic nerve stimulation at 10 Hz for 10 min. Recovery of PCr/(PCr + P(i)) ratios after exercise was fitted to a monoexponential curve. The resultant function was used to calculate the half time for PCr recovery, the initial PCr resynthesis rate, and the maximal oxidative ATP synthesis rate, which reflect the rephosphorylation of ADP and are therefore measures of mitochondrial oxidative capacity. PCr/ATP ratios decreased by 12 and 11%, 24 and 48 hr after CLP, respectively. The PCr/P(i) ratios decreased incrementally (7% in 24 degrees CLP vs 23% in 48 degrees CLP animals). Twenty-four hours after operation the half time for PCr recovery was shortened while the initial PCr resynthesis rate and maximal oxidative ATP synthesis rate were accelerated in CLP animals compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

PubMed1995

Multifrequency bioelectrical impedance fails to quantify sequestration of abdominal fluid.

Multifrequency bioelectrical impedance analysis (MFBIA) was used to determine the intracellular (ICW) and extracellular water (ECW) compartments in rats. Resistance and reactance were measured on various body segments with frequencies ranging from 1 KHz to 1 MHz. After initial measurements, 0.9% NaCl was injected intravenously or intraperitoneally, and changes in ECW and ICW were estimated by MFBIA. Important differences were found between segments. In the leg, estimated ECW increased in proportion to the volume of intravenous fluid infused, whereas estimated ICW changed minimally. However, in the trunk region, both estimated ECW and ICW were increased with intravenous and intraperitoneal injections. Our findings indicate that MFBIA has important limitations for quantifying fluid compartments in the trunk and thus in whole body, especially when applied to ill patients in whom sequestration of fluid in the trunk region frequently occurs.

Abdomen↗

PubMed1994

31P magnetic resonance spectroscopy demonstrates expansion of the extracellular space in the skeletal muscle of starved rats.

Starvation significantly alters the distribution of body water. To study the effects of starvation on cellular energetics and water distribution in skeletal muscle, a novel 31P magnetic resonance technique (31P MRS) was developed to measure water compartments. After 31P MRS-visible water space markers which distribute in total body water (dimethyl methylphosphonate, DMMP) and extracellular water (phenylphosphonate, PPA) were infused intravenously, 31P MRS spectra were obtained from the gastrocnemius muscle of male virus-free Wistar rats at baseline and after starvation or ad libitum feeding for 4 days. Muscle water spaces were also measured using the chloride method and Nernst's equation. Muscle water contents as determined by drying were equivalent in the two groups. In vivo measurements of changes in DMMP relative to all of the MRS visible phosphates also demonstrated that the total water space was similar in control and starved rats. However, starvation significantly increased the ratio of PPA/DMMP (0.67 +/- 0.05 vs 0.87 +/- 0.04, Control vs Starvation; P < 0.001), and therefore the ratio of extracellular water to total water in the gastrocnemius. Furthermore, because muscle water contents were comparable between the groups, this expansion of the extracellular space was accompanied by contraction of the intracellular compartment in starved animals. Equivalent changes were detected in vitro using the chloride method. Lastly, phosphocreatine/ATP ratios, which measured changes in high-energy phosphate stores, decreased after starvation (4.09 +/- 0.06 vs 3.61 +/- 0.06; P < 0.001) and were inversely related to changes in PPA/DMMP (r = -0.61; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1994

Glutathione deficiency accentuates hepatocellular fluid accumulation after ischemia-reperfusion.

Liver ischemia-reperfusion is known to be associated with free radical-mediated hepatocellular damage but alterations in hepatocellular fluid flux under these conditions are incompletely understood. Deficiency of the antioxidant glutathione, which increases the liver's susceptibility to ischemia-reperfusion injury, may exacerbate pathological fluid shifts. This study examined alterations in hepatic fluid dynamics during liver ischemia-reperfusion in glutathione-deficient and glutathione-replete rats. Normal and glutathione-deficient rats underwent liver ischemia-reperfusion. Changes in hepatic extra- and intracellular fluid were monitored by calculating extra- and intracellular conductance from liver multifrequency bioelectrical impedance measurements. Liver malonyl dialdehyde content and plasma transaminase concentrations were measured and correlated with changes in hepatic impedance. Hepatic extracellular conductance decreased during ischemia and returned toward baseline values during reperfusion in a similar fashion in both study groups. Intracellular conductance increased during ischemia in both groups and continued to rise during the initial phase of reperfusion before falling toward normal. Glutathione-deficient rats had a significantly higher intracellular conductance during early reperfusion compared to controls. Glutathione-depleted rats also had higher serum transaminases and liver malonyl dialdehyde content following reperfusion. Intracellular and extracellular conductance were significantly correlated with hepatic malonyl dialdehyde content. We conclude that (1) liver ischemia-reperfusion results in movement of fluid from the extracellular to intracellular space with hepatocellular swelling; (2) glutathione deficiency accentuates hepatocyte swelling following ischemia-reperfusion; and (3) changes in extra- and intracellular fluid are related to the severity of membrane damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Glutathione depletion in rats impairs T-cell and macrophage immune function.

Critical illness is associated with both immunosuppression and glutathione deficiency. We determined if in vivo depletion of glutathione would adversely affect immune status. Rats with normal glutathione levels and those with glutathione stores depleted by diethyl maleate underwent analysis of splenocyte function and mesenteric lymph node lymphocyte function. Lymphocytes of the spleen and mesenteric lymph nodes were tested for concanavalin A proliferative response and interleukin 2 production. Tumor necrosis factor and interleukin 6 secretion by splenic adherent cells was also measured. Glutathione-depleted animals had significantly decreased lymphocyte proliferation and decreased production of tumor necrosis factor and interleukin 6 but unaltered interleukin 2 production. These findings indicate that in vivo glutathione deficiency impairs macrophage and T-cell function. Because glutathione depletion may occur in sepsis, trauma, and shock, treatments that help maintain glutathione levels may enhance immunocompetence and thus improve the ability of patients to recover from critical illness.

Animals↗

PubMed1992

Glutamine preserves liver glutathione after lethal hepatic injury.

Glutathione (GSH) is a major antioxidant that protects tissues from free radical injury. Glutamine augments host defenses and may be important in GSH synthesis. Acetaminophen toxicity causes hepatic GSH depletion and hepatic necrosis. The authors hypothesized that glutamine-supplemented nutrition would enhance liver GSH stores and diminish hepatic injury and death after acetaminophen overdose. Wistar rats received either a standard total parenteral nutrition (TPN) solution (STD) or an isocaloric, isonitrogenous glutamine-supplemented solution (GLN). On the 5th day of feeding, animals were given acetaminophen (400 mg/kg intraperitoneally) and then killed at various time points. Standard TPN solution animals had a rapid depletion of hepatic glutathione, whereas GLN animals were resistant to this drop and rapidly repleted hepatic GSH stores. Glutamine-supplemented animals maintained higher plasma glutamine concentrations, had lesser elevations in hepatic enzymes, and sustained significantly fewer complications compared with STD animals. The authors conclude that glutamine-supplemented nutrition preserves hepatic glutathione, protects the liver, and improves survival during acetaminophen toxicity. Glutamine may augment host defenses by enhancing antioxidant protection.

Acetaminophen↗

PubMed1992

Glutathione deficiency increases organ dysfunction after hemorrhagic shock.

BACKGROUND: Reactive oxygen metabolites contribute to tissue destruction in a wide variety of diseases. Glutathione, a potent endogenous antioxidant, neutralizes the destructive potential of free radicals, but this tripeptide may be depleted during illness. We hypothesized that glutathione deficiency would amplify organ dysfunction after shock in rats. METHODS: Rats received either diethyl maleate to deplete tissue glutathione or a control solution intraperitoneally. The animals were subsequently bled to and maintained at a mean arterial pressure of 40 mm Hg for 30 minutes and then fully resuscitated. Sham animals underwent blood pressure monitoring only. Tissue glutathione, liver and renal function tests, organ bacterial content, and mortality rates were determined 4 and 24 hours after shock. RESULTS: Normal rats subjected to shock and sham animals had similar laboratory chemistry results, organ culture results, and mortality rates. However, glutathione-depleted animals subjected to shock had elevated liver and renal function tests, increased organ bacteria, and a dramatic increase in mortality rates compared with control shock and sham animals. CONCLUSIONS: We conclude that glutathione deficiency predisposes animals to organ failure and death after an otherwise nonlethal period of hypotension. Because glutathione deficiency is associated with severe injury and sepsis, treatment strategies that maintain glutathione stores may decrease the incidence of multisystem organ failure.

Animals↗

PubMed1991

Hepatic failure and coma after liver resection is reversed by manipulation of gut contents: the role of endotoxin.

Despite significant improvements in the surgical care of patients, hepatic failure after extensive liver resection continues to be associated with a high morbidity and death. We postulated that hepatic failure after liver resection was related to gut-derived endotoxemia. Rats were randomized to receive oral gavage twice daily with one of the following preparations: (1) 0.9% saline; (2) neomycin sulfate and cefazolin; (3) cholestyramine; (4) lactulose. After 7 days of gavage, animals underwent either a two-thirds partial hepatectomy or sham operation. At time 0 (preresection), 10, 20, and 30 hours after resection, aortic blood was obtained for determination of ammonia, glutamine, and endotoxin levels. In selected animals, portal vein or inferior caval blood was obtained simultaneously with the aortic sample to evaluate the glutamine and ammonia exchange across the intestine and hind limb. Germ-free rats also underwent a partial hepatectomy or sham operation, and blood was obtained for glutamine and ammonia exchange at 0 and 20 hours after resection. Hepatectomy in the saline-pretreated rats resulted in a sixfold increase in plasma glutamine, increased uptake of glutamine and release of ammonia by the gut, increased release of glutamine by the hind-limb, and a high mortality rate. Pretreatment with agents that altered gut contents reduced the endotoxemia, maintained normal glutamine and ammonia levels, and reduced the mortality rate. Germ-free rats had a similar response to that seen in treated animals. Altering the gut contents in this model reduced the level of endotoxemia, blunted the catabolic response, and enhanced survival.

Ammonia↗

PubMedDate not supplied

Parenteral glutathione monoester enhances tissue antioxidant stores.

Glutathione (GSH) is a potent endogenous antioxidant that protects major organs from oxidant injury. However, present nutrition regimens may inadequately support tissue stores of this tripeptide during critical illness. To determine whether GSH reserves can be enhanced in vivo with intravenous (IV) supplements, rats underwent central venous catheterization, were given chow and water ad libitum during a 2-day recovery period, and were then randomized to receive one of three treatments as an IV bolus: (1) dextrose, (2) glutathione (GSH), or (3) glutathione monoethyl ester. GSH monoethyl ester is transported into cells more easily than is GSH. Tissue and plasma samples were analyzed for GSH at 2 and 4 hours after drug administration. Liver, renal, and ileal mucosal GSH were significantly increased in the GSH-monoethyl ester rats compared with dextrose-treated animals. In addition, plasma GSH was dramatically increased after monoester injection. In contrast, GSH administration depressed liver GSH stores and did not significantly affect GSH concentration in the other organs analyzed. Plasma GSH concentration was elevated 2 hours after GSH administration. We conclude that: (1) the monoethyl ester of glutathione can be used in vivo to enhance tissue and plasma GSH concentration and (2) IV GSH administration does not significantly increase tissue GSH levels and may paradoxically depress hepatic GSH in normal rats. Because the malnourished and critically ill are likely to have depleted GSH stores, nutrition strategies that include the provision of GSH monoester may lend additional support to those organs that are at risk for injury from oxygen free radicals during catabolic states.

Animals↗